Previous work from this laboratory had delineated a number of sulfotransferases that had been purified to homogenous form from mammalian livers and characterized. In this manner, phenol sulfotransferases of different types, alcohol sulfotransferases, and an amine sulfotransferase were identified and their mechanism of catalysis examined. All of these enzymes displayed the very broad specificity for lipophilic compounds that characterizes the enzymes of detoxication, a property that is useful in correlating physical and chemical properties of substrates with the protein's catalytic effectiveness. Recently, a cDNA for tyrosine-ester sulfotransferase, has been obtained and is being expressed in large quantities by a bacterium. The resultant protein is entirely similar to the original mammalian species in catalytic capacity, although two separable protein species are obtained; no difference between the two may be due to differences in folding. Attempts at obtaining site directed mutations have led to the isolation of about a dozen single-site mutants as well as of deletions. Several of the resultant mutant enzymes have been expressed, brought to homogeneity and tested for activity with a broad range of substrates. Although this work is entirely preliminary, it is apparent that quantitative changes in substrate utilization exist and that changes in secondary structure, measured by circular dichroism, have occurred as the result of mutations.